What is the initial management of proteinuria?

Initial Management of Proteinuria

The initial management of proteinuria should begin with ACE inhibitors or ARBs for patients with proteinuria >0.5 g/day, with uptitration of the medication as tolerated to achieve proteinuria <1 g/day. 1

Assessment and Evaluation

• All patients with proteinuria should be assessed for risk of progression by evaluating proteinuria level, blood pressure, and eGFR at diagnosis and during follow-up 1
• Quantify proteinuria using spot urine protein-to-creatinine ratio when dipstick shows ≥1+ protein (roughly correlates to 30 mg/dL or protein-to-creatinine ratio ≥1300 mg/g) 1
• Renal ultrasound may provide information on kidney size, presence of stones, and extrarenal/intrarenal lesions in patients with evidence of chronic kidney disease 1
• Additional evaluations to identify the cause of proteinuria include serological tests for hepatitis B and C, complement levels, antinuclear antibody testing, cryoglobulin levels, quantitative immunoglobulin testing, and serum/urine protein electrophoresis 1

Treatment Algorithm

Step 1: Antiproteinuric and Antihypertensive Therapy

• For proteinuria >1 g/day:

  • Start long-term ACE inhibitor or ARB treatment with uptitration depending on blood pressure 1
  • Target blood pressure <125/75 mmHg 1
  • Titrate ACE inhibitor or ARB upward as far as tolerated to achieve proteinuria <1 g/day 1

• For proteinuria between 0.5-1 g/day:

  • Consider ACE inhibitor or ARB treatment 1
  • Target blood pressure <130/80 mmHg 1

Step 2: Additional Therapy for Persistent Proteinuria

• For patients with persistent proteinuria ≥1 g/day despite 3-6 months of optimized supportive care (including ACE inhibitors/ARBs and BP control) and GFR >50 mL/min per 1.73 m², consider a 6-month course of corticosteroid therapy 1

Special Considerations

• In HIV-infected patients, annual screening for proteinuria is recommended for high-risk groups: African Americans, patients with diabetes, patients with hypertension, patients with hepatitis C coinfection, and patients with HIV RNA levels ≥14,000 copies/mL or CD4+ counts <200 cells/mL 1
• Persistent proteinuria >1 g/day is associated with poorer prognosis and faster progression of kidney disease 2
• Proteinuria may be tubulotoxic and directly contribute to renal deterioration 2

Common Pitfalls and Caveats

• Transient proteinuria can occur with fever, exercise, stress, or cold exposure and resolves when the inciting factor is removed - avoid unnecessary workup in these cases 3, 4
• Orthostatic proteinuria is common in children and adolescents and is generally benign - confirm with first-morning urine sample 4
• False positive dipstick results can occur with alkaline, dilute, or concentrated urine; gross hematuria; and presence of mucus, semen, or white blood cells 3
• Small kidneys (<9 cm in length) on ultrasound may indicate advanced and irreversible kidney disease 1
• Referral to a nephrologist is recommended for patients with proteinuria >2 g/day or when the underlying etiology remains unclear after thorough evaluation 3